Cytokine gene transfer to tumor cells has been used to increase local production of these immune modulating proteins, with the aim of enhancing tumor immunogenicity and consequent host recognition and elimination of tumor (Dranoff et al. 1993; Gansbacher et al. 1992). Production of irradiated, non-dividing tumor cells secreting cytokines such as Interleukin-2 (IL-2), gamma-interferon (.gamma.-IFN), or granulocyte macrophage-colony stimulating factor (GM-CSF) represents a potential therapeutic strategy for treatment of malignant disease (Saito et al. 1994; Dranoff et al. 1993; Gansbacher et al. 1992), and one that is currently being evaluated in clinical trials (Lotze et al. 1994; Seigler et al. 1994; Rosenberg et al. 1992). Many methods have been examined for gene transfer (Davidson et al. 1993; Drazan et al. 1994; Yang et al. 1995; Paquereau & Le Cam, 1992; Jamagin et al. 1992); the most successful have been those using retroviral vectors (Dranoff et al. 1993; Gansbacher et al. 1992).
An impediment to the production of autologous tumor vaccines has been logistic problems surrounding gene transfer to freshly harvested tumors. The most widely utilized approach for gene transfer to tumors relies on retroviral vectors, which are relatively inefficient and require replicating cells for gene expression (Wilson et al. 1988). The production of an autologous vaccine using retroviral vectors requires placing harvested tumor in tissue culture before in vitro transduction, selection, and isolation of the minority of cells in which gene transfer was successful. Such a process is therefore lengthy, expensive, and fraught with technical problems of establishing and maintaining primary cell culture. These difficulties have forced investigators to examine as alternative vaccine strategies the administration of established allogeneic cytokine-secreting tumor cell lines (Patel et al. 1994), use of other vectors for gene transfer such as adenoviral vectors (Drazan et al. 1994; Yang et al. 1995), or the administration of cytokine-producing fibroblast cell lines along with the autologous tumor cells (Lotze et al. 1994).
It is an object of the present invention to provide a method for rapid production of autologous tumor vaccines which can be completed within hours, for example in less than four hours, permitting rapid treatment of tumor patients.
It is a further object of the invention to provide a method for rapid production with autologous tumor vaccines which can be applied to tumor cells in vivo without requiring surgical removal of tumor material.
It is still a further object of the present invention to provide compositions useful in the methods of the invention.